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Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin

Official URL:https://doi.org/10.1016/j.molcel.2005.06.009
PubMed:View item in PubMed
Creators Name:Ding, Q. and Xia, W. and Liu, J.C. and Yang, J.Y. and Lee, D.F. and Xia, J. and Bartholomeusz, G. and Li, Y. and Pan, Y. and Li, Z. and Bargou, R.C. and Qin, J. and Lai, C.C. and Tsai, F.J. and Tsai, C.H. and Hung, M.C.
Journal Title:Molecular Cell
Journal Abbreviation:Mol Cell
Volume:19
Page Range:159-170
Date:1 January 2005
Keywords:Amino Acid Motifs, Breast Neoplasms, Cultured Tumor Cells, Cytoskeletal Proteins, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Glycogen Synthase Kinase 3, Hepatocellular Carcinoma, Insulin-Like Growth Factor I, Liver Neoplasms, Phosphorylation, Trans-Activators, Up-Regulation, beta Catenin, erbB-2 Genes
Abstract:Beta-catenin is upregulated in many human cancers and considered to be an oncogene. Hepatocellular carcinoma (HCC) is one of the most prevalent human malignancies, and individuals who are chronic hepatitis B virus (HBV) carriers have a greater than 100-fold increased relative risk of developing HCC. Here we report a mechanism by which HBV-X protein (HBX) upregulates beta-catenin. Erk, which is activated by HBX, associates with GSK-3beta through a docking motif ((291)FKFP) of GSK-3beta and phosphorylates GSK-3beta at the (43)Thr residue, which primes GSK-3beta for its subsequent phosphorylation at Ser9 by p90RSK, resulting in inactivation of GSK-3beta and upregulation of beta-catenin. This pathway is a general signal, as it was also observed in cell lines in which Erk-primed inactivation of GSK-3beta was regulated by IGF-1, TGF-beta, and receptor tyrosine kinase HER2, and is further supported by immunohistochemical staining in different human tumors, including cancers of the liver, breast, kidney, and stomach.
ISSN:1097-2765
Publisher:Cell Press (U.S.A.)
Item Type:Article

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